Memory problems are a common complaint in the affective disorders. In work recently completed with Dr. Weingartner of the Laboratory of Psychology and Psychopathology, we were able to demonstrate close relationships among increasing severity of depression and decrements in both motor and memory tasks in affectively disordered patients. The results suggested that a deficit in the central motivational state of depressed subjects might account for their performance prolems. To expand these findings of a relationship between central motivational state and cognitive performance, we chose to look at the opiate system in man, as endogenous opiates seem to be important in the regulation of reinforcement and cognition in animals, and of mood in man. To appropriately assess the system a high dose naloxone strategy was required. At high doses (greater or equal than 2 mg/kg), naloxone increased depression and anxiety ratings in normals and produced a decrease in memory performance. The pattern of memory changes, however, was somewhat different from those predicted from our work with depressed patients.